Immune modulation by parenteral lipid emulsions.
ABSTRACT Total parenteral nutrition is the final option for nutritional support of patients with severe intestinal failure. Lipid emulsions constitute the main source of fuel calories and fatty acids (FAs) in parenteral nutrition formulations. However, adverse effects on patient outcomes have been attributed to the use of lipids, mostly in relation to impaired immune defenses and altered inflammatory responses. Over the years, this issue has remained in the limelight, also because technical advances have provided no safeguard against the most daunting problems, ie, infectious complications. Nevertheless, numerous investigations have failed to produce a clear picture of the immunologic characteristics of the most commonly used soybean oil-derived lipid emulsions, although their high content of n-6 polyunsaturated FAs (PUFAs) has been considered a drawback because of their proinflammatory potential. This concern initiated the development of emulsions in which part of the n-6 FA component is replaced by less bioactive FAs, such as coconut oil (rich in medium-chain saturated FAs) or olive oil (rich in the n-9 monounsaturated FA oleic acid). Another approach has been to use fish oil (rich in n-3 PUFA), the FAs of which have biological activities different from those of n-6 PUFAs. Recent studies on the modulation of host defenses and inflammation by fish-oil emulsions have yielded consistent data, which indicate that these emulsions may provide a tool to beneficially alter the course of immune-mediated conditions. Although most of these lipids have not yet become available on the US market, this review synthesizes available information on immunologic characteristics of the different lipids that currently can be applied via parenteral nutrition support.
SourceAvailable from: Rafat Siddiqui[Show abstract] [Hide abstract]
ABSTRACT: Background Thrombosis and immune dysfunction are two important complications that result from the administration of parenteral nutrition. Endothelial cells within the vasculature are crucial components necessary for maintenance of normal coagulation and immune function. Methods We compared the effects of three commercial lipid emulsions (LEs; Intralipid®, ClinOleic® [or Clinolipid®], and Omegaven®) differing in the levels of omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-9 monounsaturated fatty acids, and saturated fatty acids upon endothelial cell fatty acid composition using Gas chromatography, endothelial cell integrity by assessing measurement of apoptosis and necrosis using flow cytometry, endothelial cell inflammatory activation by assessing the induction of ICAM-1 by lipopolysaccharide [LPS]), and transcription factor activation (phosphorylation of NF-κB) using western blot analysis. Results Gas chromatographic analysis confirmed cellular uptake of the fatty acids within the LEs; furthermore, these fatty acid changes reflected the composition of the oils and egg phosphatides used in the manufacturing of these emulsions. However, the kinetics of fatty acid uptake and processing differed between LEs. Fish oil LE negatively impacted cell viability by doubling the percentage of apoptotic and necrotic cell populations quantified by flow cytometry using Annexin V/Fluorescein and propidium iodide. The soybean oil LE did not alter cell viability, while the olive oil-predominate emulsion improved cell viability. All LEs were capable of suppressing LPS-induced ICAM-1 expression; however, the fish oil LE was more potent than the other emulsions. Fish oil LE supplementation of cells also suppressed LPS-induced phosphorylation of NF-κB, while the soybean oil and olive predominant LE had no effect upon NF-κB phosphorylation. Conclusions Lipid emulsions are readily incorporated and stored in the form of triacylglycerols. Soybean oil-based, olive oil-predominant and fish-oil based LEs differentially affected endothelial cell integrity. Importantly, these three LEs were capable of suppressing endothelial cell inflammatory response despite their fatty acid content.Lipids in Health and Disease 12/2015; 14(1). DOI:10.1186/s12944-015-0005-6 · 2.31 Impact Factor
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ABSTRACT: Intravenous fish oil (FO) lipid emulsions (LEs) are rich in ω-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and immunomodulatory effects. We previously demonstrated that FO containing emulsions may be able to decrease mortality and ventilation days in the critically ill. Over the last year, several additional randomized controlled trials (RCTs) of FO containing emulsions have been published. Therefore, the purpose of this systematic review was to update our systematic review aimed to elucidate the efficacy of FO-containing emulsions on clinical outcomes in the critically ill. We searched computerized databases from 1980 to 2014. We included 4 new RCTs conducted in critically ill adult patients that evaluated FO containing emulsions in parenterally or enterally fed patients. A total of 10 RCTs (n = 733) met inclusion criteria. The mean methodological score was 8 (range, 3-12). No effect on overall mortality was found. When the results of 5 RCTs that reported infections were aggregated, FO containing emulsions significantly reduced infections (RR 0.64; 95% CI, 0.44-0.92; P = 0.02, heterogeneity I (2) = 0%). Subgroup analysis demonstrated that predominantly enteral nutrition (EN) based trials showed a tendency towards a reduction in mortality (RR 0.69; 95% CI, 0.40-1.18, P = 0.18, heterogeneity I (2) = 35%). High quality trials showed a significant reduction in hospital length of stay (LOS) (WMD -7.42; 95% CI, -11.89, -2.94, P = 0.001) although low quality trials had no effect (P = 0.45); test for subgroup differences on hospital LOS was significant (P = 0.001). FO containing emulsions may be associated with a reduction in infections, as well as could be associated with a reduction in duration of ventilation and hospital length of stay. Further large scale RCTs, which should aim to consolidate potential positive treatment effects, are warranted.Critical care (London, England) 04/2015; 19(1):167. DOI:10.1186/s13054-015-0888-7
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ABSTRACT: Introduction: Parenteral nutrition (PN) in preterm infants leads to PN-associated liver disease (PNALD). PNALD has been linked to serum accumulation of phytosterols that are abundant in plant oil but absent in fish oil emulsions. Hypothesis: Whether modifying the phytosterol and vitamin E composition of soy and fish oil lipid emulsions affects development of PNALD in preterm pigs. Methods: We measured markers of PNALD in preterm pigs that received 14 days of PN that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2) Intralipid + vitamin E (ILE, d-α-tocopherol), (3) Omegaven (OV, 100% fish oil), or (4) Omegaven + phytosterols (PS, β-sitosterol, campesterol, and stigmasterol). Results: Serum levels of direct bilirubin, gamma glutamyl transferase, serum triglyceride, low-density lipoprotein, and hepatic triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS compared to IL. Hepatic cholesterol 7-hydroxylase and organic solute transporter-α expression was lower (P < .05) and portal plasma FGF19 higher in the ILE, OV, and PS vs IL. Hepatic expression of mitochondrial carnitine palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation genes was higher in ILE, OV, and PS vs IL. In vivo (13)C-CDCA clearance and expression of pregnane X receptor target genes, cytochrome P450 3A29 and multidrug resistance-associated protein 2, were higher in ILE, OV, and PS vs IL. Conclusions: α-tocopherol in Omegaven and added to Intralipid prevented serum and liver increases in biliary and lipidemic markers of PNALD in preterm piglets. The addition of phytosterols to Omegaven did not produce evidence of PNALD. © 2015 American Society for Parenteral and Enteral Nutrition.Journal of Parenteral and Enteral Nutrition 01/2015; DOI:10.1177/0148607114567900 · 3.14 Impact Factor